title: A five-alpha reductase inhibitor or an antiandrogen prevents the progression of microscopic prostate carcinoma to macroscopic carcinoma in rats.
abstract: BACKGROUND
  The objective of this study was to elucidate the prophylactic effects of 5-alpha reductase inhibitor (e.g., finasteride) and a pure antiandrogen (e.g., casodex) on rat prostate carcinogenesis and to determine whether latent prostate carcinoma can be prevented to develop to clinically significant cancer by use of these drugs.
  
  
  METHODS
  F344 rats were subcutaneously administered 3,2'-dimethyl-4-aminobiphenyl (DMAB) for the first 20 weeks and testosterone propionate throughout the 60-week study. Finasteride (5 mg/kg and 15 mg/kg, 2 times per week) and casodex (15 mg/kg, 30 mg/kg, and 60 mg/kg, 3 times per week) were administered orally during the last 40 weeks of the study. Tumors were classified as visible prostate carcinoma when they could be recognized with the naked eye and as microscopic prostate carcinoma when detectable only with a microscope.
  
  
  RESULTS
  The incidence of visible prostate carcinoma was 51% (18 of 35 rats) in the positive control group, whereas it was 40% (4 of 10 rats) in the finasteride 5 mg/kg group, 16.7% (2 of 12 rats, P = 0.0091) in the finasteride 15 mg/kg group, 20% (4 of 20 rats, P = 0.05) in the casodex 15 mg/kg group, 14.3% (3 of 21 rats, P = 0.0008) in the casodex 30 mg/kg group, and 0% (0 of 11 rats, P = 0.0002) in the casodex 60 mg/kg group. On the other hand, when visible carcinomas and microscopic carcinomas were handled together, only casodex 60 mg/kg significantly inhibited the carcinogenesis rate.
  
  
  CONCLUSIONS
  Finasteride achieved dose-dependent inhibition of macroscopic rat prostate carcinogenesis, and casodex also inhibited macroscopic prostate carcinogenesis. However, both drugs showed insufficient prevention of carcinogenesis at the microscopic level. These findings indicate that, in clinical medicine as well, such drugs may also be able to prevent the progression of latent prostate carcinoma to life-threatening disease.
authors.affiliation: Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tsukamoto
authors.forename: H
authors.initials: H
authors.lastname: Akaza
authors.forename: M
authors.initials: M
authors.lastname: Onozawa
authors.forename: T
authors.initials: T
authors.lastname: Shirai
authors.forename: Y
authors.initials: Y
authors.lastname: Ideyama
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000494:pharmacology*; D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology*; D000611:Aminobiphenyl Compounds; D000726:Androgen Antagonists / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D002273:Carcinogens; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018120:Finasteride / Q000494:pharmacology*; D008297:Male; D009570:Nitriles; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D013739:Testosterone; D014105:Tosyl Compounds
chemical_list: D000611:Aminobiphenyl Compounds; D000726:Androgen Antagonists; D000813:Anilides; D002273:Carcinogens; D004791:Enzyme Inhibitors; D009570:Nitriles; D014105:Tosyl Compounds; C001042:2',3-dimethyl-4-aminobiphenyl; D013739:Testosterone; D018120:Finasteride; C053541:bicalutamide; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase